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ObjectiveMany persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood.Method and participantsStudy participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time.ResultsHPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14.ConclusionsWorsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation.

Pregnancy in women living with human immunodeficiency virus (WLWH) represents an important challenge for maternal-fetal health. Besides, they can also present anxiety (Anx) and depression (Dep). Imbalances in serotonin (5-HT), dehydroepiandrosterone sulfate (DHEA-S), and cortisol (CORT) levels can contribute to Anx and Dep manifestations. Currently, there is not enough data about the neuroendocrine and neurochemical changes in pregnant WLWH with affective disorders. This study aimed to characterize 5-HT, DHEA-S, and CORT plasma levels in Mexican pregnant WLWH presenting Anx/Dep. Forty-two adult pregnant women were recruited during the third trimester of gestation at the National Institute of Perinatology in Mexico during 2019–2022. These patients were divided into three groups: (1) pregnant WLWH with Anx/Dep (n = 16), (2) pregnant without HIV but with Anx/Dep (n = 12), and (3) healthy pregnant women without Anx/Dep (n = 14). WLWH presented a marked reduction in 5-HT (41.33 ± 39.37 ng/dL) compared to non-infected pregnant women with Anx/Dep (220.2 ± 151.8 ng/dL) and the healthy group (370.0 ± 145.3 ng/dL). Anx/Dep infected and uninfected pregnant women showed a significant reduction in DHEA-S levels (86.58 ± 30.59 and 76.9 ± 36.7 µg/dL, respectively) compared to healthy subjects (149.7 ± 44.6 µg/dL). Anx and Dep symptoms were inversely correlated with 5-HT and DHEA-S levels. No significant differences were observed in CORT levels among the three groups (p = 0.094). Our results suggest the presence of a disbalance in 5-HT and DHEA-S levels in pregnant WLWH with affective symptoms. [ABSTRACT FROM AUTHOR]

BackgroundIndividuals with depression symptoms have a harder time quitting smoking. High negative affect and low positive affect are core depression symptoms and arise following cigarette abstinence. Investigating associations of biological markers with negative and positive affect may provide valuable information about factors relevant to smoking cessation in individuals with elevated depression symptoms.MethodsDepression symptoms were measured at a baseline session. Participants then completed two counterbalanced experimental sessions (non-abstinent, abstinent) and completed measures of positive and negative affect, and provided saliva samples. Saliva samples were assayed at the Salimetrics' SalivaLab (Carlsbad, CA) using the Salimetrics Salivary Dehydroepiandrosterone (DHEA) Assay Kit (Cat. No. 1-1202) and Dehydroepiandrosterone-sulfate (DHEA-S) Assay Kit (Cat. No. 1-1252).ResultsThere were no main or interactive associations of DHEA with negative affect. However, there were significant DHEAS × experimental session and DHEAS × experimental session × depression symptom level interactions with negative affect. In the high depression symptom group, DHEAS positively associated with negative affect during the non-abstinent experimental session, but DHEAS negatively associated with negative affect during the abstinent experimental session. There were no associations of DHEA or DHEAS with positive affect.ConclusionThis study found that DHEAS negatively associated with negative affect during cigarette abstinence in individuals with elevated depression symptoms. This is important as high negative affect during cigarette abstinence may result in a return to smoking.

Neuronal Kv7 voltage-gated potassium channels generate the M-current and regulate neuronal excitability. Here, we report that dehydroepiandrosterone sulfate (DHEAS) is an endogenous Kv7 channel modulator that attenuates Gq-coupled receptor-induced M-current suppression. DHEAS reduced muscarinic agonist-induced Kv7-current suppression of Kv7.1, Kv7.2, Kv7.4, or Kv7.5 homomeric currents and endogenous M-currents in rat sympathetic ganglion neurons. However, DHEAS per se did not alter the voltage dependence of these Kv7 homomeric channels or the m1 receptor-induced activation of phospholipase C or protein kinase C. DHEAS-treated Kv7.2 homomeric currents became resistant to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) induced by voltage-activated phosphatase, Ci-VSP or eVSP. Our computational models predicted a novel binding site for DHEAS in the cytoplasmic domain of Kv7 subunits. A single-point mutation of the predicted key histidine into cysteine in the rat Kv7.2 subunit, rKv7.2(H558C), resulted in a loss of effects of DHEAS on muscarinic Kv7 current suppression. Furthermore, in vivo administration of DHEAS in mice of both sexes reduced late phase pain responses in the formalin paw test. However, it did not have effects on early phase responses in the formalin paw test or responses in the hot plate test. Coadministration of a selective Kv7 inhibitor, XE991, and DHEAS eliminated analgesic effects of DHEAS in late phase responses in the formalin paw test. Collectively, these results suggest that DHEAS attenuates M-current suppression by stabilizing PIP2-Kv7 subunit interaction and can mitigate inflammatory pain.SIGNIFICANCE STATEMENT M-current suppression induced by stimulation of Gq-coupled receptors is a form of Kv7 current modulation that can reversibly increase neuronal excitability. This study demonstrates that DHEAS, an endogenous steroid hormone, is a novel Kv7 channel modulator that can attenuate M-current suppression without affecting basal Kv7 channel kinetics. Administration of DHEAS in vivo alleviated inflammatory pain in rodents. These results suggest that the degree of M-current suppression can be dynamically regulated by small molecules. Therefore, this novel form of Kv7 channel regulation holds promising potential as a therapeutic target for sensitized nervous activities, such as inflammatory pain.

Introduction: This study is to investigate the relation between serum dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) levels and the risk of osteoporosis in patients with T2DM. Materials and Methods: This cross-sectional study involved 938 hospitalized patients with T2DM. Linear regression models were used to explore the relationship between DHEA and DHEAS and the BMD at different skeletal sites. Multinominal logistic regression models and the restricted cubic spline (RCS) were used to evaluate the associations of DHEA and DHEAS with the risks of osteopenia and/or osteoporosis. Results: In postmenopausal women with T2DM, after adjustment for confounders including testosterone and estradiol, DHEA showed a significant positive correlation with lumbar spine BMD (P = 0.013). Moreover, DHEAS exhibited significant positive correlations with BMD at three skeletal sites: including femoral neck, total hip, and lumbar spine (all P < 0.05). Low DHEA and DHEAS levels were associated with increased risk of osteopenia and/or osteoporosis (all P < 0.05) and the risk of osteoporosis gradually decreased with increasing DHEAS levels (P overall = 0.018, P-nonlinear = 0.559). However, DHEA and DHEAS levels in men over the age of 50 with T2DM were not associated with any of above outcomes. Conclusion: In patients with T2DM, independent of testosterone and estradiol, higher DHEA and DHEAS levels are associated with higher BMD and lower risk of osteopenia/osteoporosis in postmenopausal women but not men over the age of 50. [ABSTRACT FROM AUTHOR]

Current liquid chromatography-tandem mass spectrometry (LC-MS/MS) applications for circulating androgen measurements are technically diverse. Previously, variable results have been reported for testosterone. Data are scarce for androstenedione and absent for dehydroepiandrosterone sulfate (DHEAS). We assessed the agreement of androstenedione, DHEAS and testosterone LC-MS/MS measurements among nine European centers and explored benefits of calibration system unification. Androgens were measured twice by laboratory-specific procedures in 78 patient samples and in EQA materials. Results were obtained by in-house and external calibration. Intra- and inter-laboratory performances were valued. Intra-laboratory CVs ranged between 4.2–13.2 % for androstenedione, 1.6–10.8 % for DHEAS, and 4.3–8.7 % and 2.6–7.1 % for female and male testosterone, respectively. Bias and trueness in EQA materials were within ±20 %. Median inter-laboratory CV with in-house vs. external calibration were 12.0 vs. 9.6 % for androstenedione (p<0.001), 7.2 vs. 4.9 % for DHEAS (p<0.001), 6.4 vs. 7.6 % for female testosterone (p<0.001) and 6.8 and 7.4 % for male testosterone (p=0.111). Median bias vs. all laboratory median with in-house and external calibration were −13.3 to 20.5 % and −4.9 to 18.7 % for androstenedione, −10.9 to 4.8 % and −3.4 to 3.5 % for DHEAS, −2.7 to 6.5 % and −11.3 to 6.6 % for testosterone in females, and −7.0 to 8.5 % and −7.5 to 11.8 % for testosterone in males, respectively. Methods showed high intra-laboratory precision but variable bias and trueness. Inter-laboratory agreement was remarkably good. Calibration system unification improved agreement in androstenedione and DHEAS, but not in testosterone measurements. Multiple components, such as commutability of calibrators and EQA materials and internal standard choices, likely contribute to inter-laboratory variability. [ABSTRACT FROM AUTHOR]

Background The intricate interplay between work-related stress and its physiological impact has drawn extensive research attention. Dehydroepiandrosterone sulphate (DHEA-S) emerges as a potential biomarker reflecting stress-related endocrine changes. Aims This cross-sectional study aimed to examine the association between job demands and DHEA-S levels among healthcare workers. The study also explored potential correlations between DHEA-S levels and psychophysical symptoms commonly linked to work-related stress. Methods A sample of 488 healthcare workers from a local health authority participated. Job demands were measured using the Demands scale of the Health and Safety Management Standards Indicator Tool. DHEA-S levels and symptom prevalence were assessed through serum analysis and questionnaires, respectively. Results Workers exposed to high job demands exhibited significantly lower DHEA-S levels compared to those with low job demands. Psychophysical symptoms, including sleep disorders, depression, and headache, were more prevalent in the high-demands group. DHEA-S levels showed significant negative correlations with the prevalence of all considered symptoms. Conclusions The study shows the inverse relationship between job demands and DHEA-S levels among healthcare workers, indicating that high job demands correlate with reduced DHEA-S secretion and increased symptom prevalence. The findings suggest DHEA-S as a potential biomarker for assessing the physiological consequences of work-related stress. Proactive interventions in managing job demands are crucial for promoting employee well-being and productivity in demanding work environments. By recognizing DHEA-S as a stress biomarker, organizations can effectively address stress-related health risks and implement targeted interventions for enhancing employees' overall health and work performance. [ABSTRACT FROM AUTHOR]

Background: In individuals with coronavirus disease 2019 (COVID-19), male subjects have consistently beenlinked to poor severity and prognosis. Data on sex hormones in non-critical COVID-19-infected patients are scarce.The aim of this study was to assess the status of total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS)among noncritical patients with COVID-19 according to sex and their associations with clinical and biochemicalfeatures.Materials and Methods: This cross-sectional observational study was done in the COVID-19 unit of a Universityhospital during the period of September 2021 to February 2022 among 91 adults (18-65 years) with reverse transcriptase-polymerase chain reaction confirmed noncritical COVID-19 patients. Blood was drawn by venipuncturebefore receiving steroids between 07:00 to 09:00 a.m. in a fasting state to measure serum TT and DHEAS by chemiluminescentmicroparticle immunoassay. Diagnosis and classification of COVID-19 were done according to WorldHealth Organization’s interim guidance. Age- and sex-specific laboratory reference values were used to classify theTT and DHEAS status of the patients.Results: Only three males (8.1%) had low TT and the rest had normal TT. On the other hand, 15 (27.8%) of the femaleshad high TT with normal levels in the rest. Similarly, 11 (29.7%) males had low DHEAS. Females had low, normal,and high DHEAS in four (7.4%), 48 (88.9%), and two (3.7%) cases respectively. Males with moderate severity ofCOVID-19 had significantly lower DHEAS (post hoc P=0.038) than the mild group. Both TT (P=0.008) and DHEAS(P=0.023) significantly correlated with neutrophils/lymphocytes ratio and only DHEAS with platelets/lymphocytesratio (P=0.044) in males. In females, TT significantly correlated with serum sodium (P=0.034).Conclusion: In noncritical COVID-19 patients, substantial gender variations in TT and DHEAS were detected andcorrelated with severity markers in males.

Background: In individuals with coronavirus disease 2019 (COVID-19), male subjects have consistently been linked to poor severity and prognosis. Data on sex hormones in non-critical COVID-19-infected patients are scarce. The aim of this study was to assess the status of total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS) among noncritical patients with COVID-19 according to sex and their associations with clinical and biochemical features. Materials and Methods: This cross-sectional observational study was done in the COVID-19 unit of a University hospital during the period of September 2021 to February 2022 among 91 adults (18-65 years) with reverse transcriptase- polymerase chain reaction confirmed noncritical COVID-19 patients. Blood was drawn by venipuncture before receiving steroids between 07:00 to 09:00 a.m. in a fasting state to measure serum TT and DHEAS by chemiluminescent microparticle immunoassay. Diagnosis and classification of COVID-19 were done according to World Health Organization's interim guidance. Age- and sex-specific laboratory reference values were used to classify the TT and DHEAS status of the patients. Results: Only three males (8.1%) had low TT and the rest had normal TT. On the other hand, 15 (27.8%) of the females had high TT with normal levels in the rest. Similarly, 11 (29.7%) males had low DHEAS. Females had low, normal, and high DHEAS in four (7.4%), 48 (88.9%), and two (3.7%) cases respectively. Males with moderate severity of COVID-19 had significantly lower DHEAS (post hoc P=0.038) than the mild group. Both TT (P=0.008) and DHEAS (P=0.023) significantly correlated with neutrophils/lymphocytes ratio and only DHEAS with platelets/lymphocytes ratio (P=0.044) in males. In females, TT significantly correlated with serum sodium (P=0.034). Conclusion: In noncritical COVID-19 patients, substantial gender variations in TT and DHEAS were detected and correlated with severity markers in males. [ABSTRACT FROM AUTHOR]

Objective: Sex steroid hormones are associatedwith the advancement ofmetabolic diseases such as dyslipidemia. This cross-sectional study aimed to investigate the relationship between dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels and the risk of dyslipidemia in people with type 2 diabetes mellitus. Materials and Methods: The analysis included 1,927 patients with type 2 diabetes mellitus. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels were determined using lipid chromatography-tandem mass spectrometry. Multivariable analyses were performed to investigate the association between the variables and dyslipidemia. Results: The multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) of dyslipidemia across DHEA tertiles were 0.39 and 0.24-0.64, respectively (p trend = 0.001). This relationship was still maintained when analyzed as a continuous variable (odds ratio, 0.96; 95% confidence interval, 0.92-0.99; P < 0.01). However, in males with type 2 diabetes mellitus, no significant correlations were found between rising levels of dehydroepiandrosterone sulfate, androstenedione, and total testosterone and the risk of dyslipidemia (all P > 0.05). Furthermore, there was no significant association between androgen precursors and total testosterone with regard to the risk of developing dyslipidemia (all P > 0.05). Conclusions: Serum dehydroepiandrosterone levels were substantially and adversely correlated with dyslipidemia in adult men with T2DM. These results indicated that dehydroepiandrosterone may have an essential role in the development of dyslipidemia. More prospective research is required to validate this link. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic liver disease and decompensated cirrhosis are associated with serious complications; spontaneous bacterial peritonitis is considered one of them that may lead to sepsis and adrenal insufficiency. This trial aimed to study the role of dehydroepiandrosterone sulfate (DHEAS) and DHEAS/cortisol ratio for assessing cirrhotic patients’ adrenal function and as a possible prognostic factor in cirrhotic cases with spontaneous bacterial peritonitis (SBP). Patients and methods It was a prospective cohort trial carried out on 100 patients in the Internal Medicine Department, Tanta University Hospital, from June 2021 to July 2022 divided into 2 studied patient groups: group I, 50 cases with liver cirrhosis and sterile ascites; and group II, 50 cases with liver cirrhosis and SBP. Adrenal function was evaluated using serum cortisol levels (9 A.M, 9 P.M, and post synacthen stimulation test), DHEAS level, and DHEAS/cortisol ratio. Results The cirrhotic patients with SBP have significantly decreased DHEAS, decreased DHEAS/cortisol ratio, and high cortisol level post stimulation compared with patients with sterile ascites, cirrhotic cases with decreased DHEAS/cortisol ratio (

Abstract Background Numerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children. Methods The present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children’s Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases. Results After adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36–0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01–4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases. Conclusions The current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children.

The purpose of this study is to elucidate how patient-reported cognitive symptoms manifest from variations in hormone levels or precursors such as dehydroepiandrosterone (DHEA) and its sulfated form [collectively termed as DHEA(S)] and to investigate their association in breast cancer survivors. Levels of estradiol and DHEA(S) were compared between early-stage breast cancer patients with and without cancer-related cognitive impairment (CRCI) during adjuvant chemotherapy. Data were analyzed from 242 patients (mean age ± SD = 50.8 ± 9.2 years) who had completed FACT-Cog v.3.0, blood draws and questionnaires. Regression model was used to fit the magnitude of change in each respective biomarker levels against overall cognitive impairment status while adjusting for clinically important covariates. There was reduction in mean plasma levels of estradiol and DHEAS during and towards the end of chemotherapy (p-values

Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. Although skeletal muscle disorders are often found in diabetic people, the clinical significance of DHEAS in skeletal muscle remains unclear. Therefore, we aimed to determine whether DHEAS is associated with the development of skeletal muscle disorders in individuals with type 2 diabetes (T2D). A cross-sectional study was conducted in 361 individuals with T2D. Serum DHEAS levels, skeletal muscle mass index (SMI), handgrip strength (HS), and gait speed (GS) were measured in the participants. Pre-sarcopenia, sarcopenia, and dynapenia were defined according to the definitions of the AWGS 2019 criteria. DHEAS level was positively associated with HS but not with SMI or GS after adjustment of confounding factors. Multiple logistic regression analyses in total subjects showed that DHEAS level had an inverse association with the prevalence of dynapenia but not with the prevalence of pre-sarcopenia or sarcopenia. Furthermore, a significant association between DHEAS level and dynapenia was found in males but not in females. ROC curve analysis indicated that cutoff values of serum DHEAS for risk of dynapenia in males was 92.0 μg/dL. Therefore, in male individuals with T2D who have low serum levels of DHEAS, adequate exercise might be needed to prevent dynapenia. [ABSTRACT FROM AUTHOR]

Background: Chronic liver disease and decompensated cirrhosis are associated with serious complications; spontaneous bacterial peritonitis is considered one of them that may lead to sepsis and adrenal insufficiency. This trial aimed to study the role of dehydroepiandrosterone sulfate (DHEAS) and DHEAS/cortisol ratio for assessing cirrhotic patients' adrenal function and as a possible prognostic factor in cirrhotic cases with spontaneous bacterial peritonitis (SBP). Patients and methods: It was a prospective cohort trial carried out on 100 patients in the Internal Medicine Department, Tanta University Hospital, from June 2021 to July 2022 divided into 2 studied patient groups: group I, 50 cases with liver cirrhosis and sterile ascites; and group II, 50 cases with liver cirrhosis and SBP. Adrenal function was evaluated using serum cortisol levels (9 A.M, 9 P.M, and post synacthen stimulation test), DHEAS level, and DHEAS/cortisol ratio. Results: The cirrhotic patients with SBP have significantly decreased DHEAS, decreased DHEAS/cortisol ratio, and high cortisol level post stimulation compared with patients with sterile ascites, cirrhotic cases with decreased DHEAS/cortisol ratio (< 0.65) had elevated C-reactive protein (CRP) levels, a higher model for end-stage liver disease (MELD) score and Child–Pugh score had higher hospital mortality. Both DHEAS and the DHEAS/cortisol ratio were significant predictors of hospital mortality (area under the receiver operating characteristic curve 0.267 and 0.298, respectively). The cirrhotic patients with SBP had decreased DHEAS and DHEAS/cortisol ratio but higher hospital mortality, compared to the cirrhotic patients with sterile ascites. Conclusions: It was found that a significant increase in cortisol level was after synacthen stimulation, decreased DHEAS, and low DHEAS to cortisol ratio in the cirrhotic patients with spontaneous bacterial peritonitis and was associated with high mortality compared to cirrhotic patients without spontaneous bacterial peritonitis. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the Thank You, Sorry, Love (TSL) program's effect on child abuse and the levels of oxidative stress hormone (cortisol, dehydroepiandrosterone sulfate) among North Korean refugee parents. Method: The participants, North Korean refugees (N = 45), were assigned to an experimental group with 10 sessions of TSL program intervention (n = 15), a comparison group with 10 sessions of Program A intervention (n = 15), or a control group with no intervention (n = 15). Effectiveness tests included a pre-test, post-test, and 4-week follow-up test. Results: Child abuse scores and cortisol levels differed significantly between the groups in the post-test and follow-up tests. It was confirmed that the group in the TSL program showed statistically significant improvements in child abuse and cortisol compared to the other groups. Conclusion: The TSL program can be used as a practical intervention to prevent child abuse in North Korean refugee families. [ABSTRACT FROM AUTHOR]

Background: Numerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children. Methods: The present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children's Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases. Results: After adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36–0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01–4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases. Conclusions: The current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children. [ABSTRACT FROM AUTHOR]

Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied in human airways.Objectives: To measure whether AR and its ligands are associated with human asthma outcomes.Methods: We compared the effects of AR expression on lung function, symptom scores, and fractional exhaled nitric oxide (FeNO) in adults enrolled in SARP (Severe Asthma Research Program). The impact of sex and of androgens on asthma outcomes was also evaluated in the SARP with validation studies in the Cleveland Clinic Health System and the NHANES (U.S. National Health and Nutrition Examination Survey).Measurements and Main Results: In SARP (n = 128), AR gene expression from bronchoscopic epithelial brushings was positively associated with both FEV1/FVC ratio (R2 = 0.135, P = 0.0002) and the total Asthma Quality of Life Questionnaire score (R2 = 0.056, P = 0.016) and was negatively associated with FeNO (R2 = 0.178, P = 9.8 × 10-6) and NOS2 (nitric oxide synthase gene) expression (R2 = 0.281, P = 1.2 × 10-10). In SARP (n = 1,659), the Cleveland Clinic Health System (n = 32,527), and the NHANES (n = 2,629), women had more asthma exacerbations and emergency department visits than men. The levels of the AR ligand precursor dehydroepiandrosterone sulfate correlated positively with the FEV1 in both women and men.Conclusions: Higher bronchial AR expression and higher androgen levels are associated with better lung function, fewer symptoms, and a lower FeNO in human asthma. The role of androgens should be considered in asthma management.

Background. Clinical trials showed a number of additional phenotypes of metabolic syndrome. All of them differ in the type of metabolic disorders and the composition of subcutaneous and visceral adipose tissue. Some of phenotypes have a number of clinical and metabolic similarities with endogenous or exogenous hypercorticism syndromes. The purpose was to characterize the functional activity of the adrenal glands in type 2 diabetes depen­ding on the phenotypic features: the degree of general obesity and the level of visceral fat. Material and methods. Our trial included 89 patients with type 2 diabetes (46 men and 43 women) aged 32 to 85 years. The examination included evaluation of anthropometric parameters, body composition by the bioelectrical impedance method, assessment of the lipid and carbohydrate metabolism, the level of cortisol, dehydroepiandrosterone sulfate (DHEAS) in blood serum, and the activity of 11-beta-hydroxysteroid dehydrogenase (11β-HSD) enzyme. Results. Insulin and C-peptide levels were significantly lower in the non-obese group. The cortisol/DHEAS ratio was elevated in both subgroups with high levels of visceral fat as possible marker of imbalance of anabolic and catabolic hormones. In addition, the concentration of the cortisol, measured in the blood serum of the patients after waking up, was within the normal range. However, the average value in both groups was closer to its upper ranges. This may suggest the presence of subclinical hypercortisolism caused by an increased activity of 11β-HSD, which contributes to the local production of cortisol in visceral adipose tissue. Conclusions. The hormonal and metabolic changes that we found in our groups of patients with type 2 diabetes may indicate anabolic-catabolic imbalance, which is manifested both in the features of the topography of adipose tissue and in changes of metabolic processes, i.e. form the special metabolic phenotype with a catabolic or anabolic axis. Detection the subgroups at high risk allows to develop pathogenetic approaches to the most targeted comprehensive correction of existing violations.

There is growing evidence for the involvement of sex hormones in the pathogenesis of keratoconus. This study aimed to evaluate serum androgen and prolactin levels in patients suffering from keratoconus. One hundred and two subjects were enrolled in the keratoconus (76 patients) and control (26 subjects) groups in a cross-sectional survey. Topographic evaluation of the cornea was undertaken for all enrolled participants. Serum testosterone, dehydroepiandrosterone sulphate (DHEAS), prolactin (PRL), luteinising hormone (LH), and follicle-stimulating hormone (FSH) were measured in all subjects. There was no significant difference in demographic characteristics between the study groups. Significantly higher mean serum levels of DHEAS (3.71 ± 2.23 vs. 2.53 ± 1.77 µg/mL; P = 0.009) and T (6.18 ± 3.80 vs. 1.57 ± 1.76 ng/mL; P < 0.001) were observed in men with keratoconus compared to controls. In females, there were also higher mean levels of DHEAS (2.40 ± 1.57 vs. 2.18 ± 0.72 µg/mL; P = 0.355) and T (0.78 ± 0.96 vs. 0.32 ± 0.13 ng/mL; P < 0.001) in patients with keratoconus but only T level reached the statistically significant level of difference. Also, the mean serum PRL level was significantly higher in women with keratoconus compared to control (13.33 ± 17.85 vs. 4.63 ± 3.10 ng/mL; P < 0.001). There was no significant difference between serum FSH and LH levels between study groups. In patients with keratoconus, serum PRL in females and serum androgen levels in both genders are elevated. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that affects 8–13% of women of reproductive age. It is one of the most common causes of infertility and is associated with hyperandrogenism in the form of hirsutism and acne, non-ovulatory cycles, and characteristic ovarian morphology. The available research on serum vitamin D deficiency in patients with PCOS and the appropriateness of vitamin D supplementation in this group of women is inconclusive, so we decided to investigate the influence of vitamin D on the incidence of metabolic syndrome and hormonal balance in patients with polycystic ovary syndrome. The study comprised 120 women aged between 18 and 42 years, who were divided into two groups: a group with diagnosed polycystic ovary syndrome (PCOS) and a group of regularly menstruating women without features of androgenisation, in whom polycystic ovary syndrome was excluded. Each patient underwent a history and physical examination, including a gynecological examination, anthropometric measurements were taken, including height, weight, waist, and hip circumference, and blood pressure was measured using the Korotkow method. In the female patients, the following parameters were also determined from the blood: follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, TSH, ft4, prolactin (PRL), total testosterone, DHEASO4, 17-hydroxyprogesterone (17-OHP), sex-hormone-binding globulin (SHBG), androstendione, 25(OH) vitamin D3 metabolite. The majority of the patients with polycystic ovary syndrome were found to have deficient or suboptimal serum vitamin D levels, and the effects of vitamin D on the SHBG levels and free-androgen indices in these patients was examined. The effects of vitamin D on the incidence of metabolic syndrome and BMI, waist-to-hip ratio, waist circumference, and blood pressure in patients with polycystic ovary syndrome were also found. [ABSTRACT FROM AUTHOR]

The adrenal steroid hormones, cortisol and dehydroepiandrosterone sulfate (DHEAS), are associated with the immune system in opposite actions. This study aimed to investigate the relationship between cortisol and DHEAS serum concentrations, their ratio (CDR), and natural killer cell activity (NKA). This cross-sectional study included 2275 subjects without current infection or inflammation in the final analyses. NKA was estimated by measuring the amount of interferon-gamma (IFN-γ) released by activated natural killer cells; low NKA was defined as IFN-γ level < 500 pg/mL. Cortisol, DHEAS levels, and CDRs were categorized by quartiles in men, premenopausal women, and postmenopausal women. Compared with the lowest quartile as reference, the adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for low NKA of the highest cortisol and CDR group were 1.66 (1.09–2.51) and 1.68 (1.11–2.55) in men, 1.58 (1.07–2.33) and 2.33 (1.58–3.46) in premenopausal women, and 2.23 (1.28–3.87) and 1.85 (1.07–3.21) in postmenopausal women. Only in premenopausal women, the highest DHEAS group showed significantly lower risk of low NKA (OR: 0.51, 95% CI: 0.35–0.76). HPA axis activation indicated as high cortisol level, CDR was significantly associated with low NKA, while high DHEAS levels were inversely associated with low NKA in premenopausal women. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess whether size for gestational age and dehydroepiandrosterone sulfate (DHEAS) are associated with cardiometabolic risk in central precocious puberty (CPP) girls. Methods: The retrospective study included 443 patients with newly diagnosed CPP. Subjects were categorized by birth weight for gestational age (appropriate [AGA], small [SGA], and large [LGA] for gestational age) and serum DHEAS concentration (high [≥75th percentile] and normal [<75th percentile] DHEAS). Cardiometabolic parameters were examined. Composite cardiometabolic risk (CMR) score was calculated based on BMI, blood pressure, glucose, insulin, triglyceride, and HDL cholesterol. Non-obesity CMR score was computed, omitting the value from BMI. Logistic regression models, general linear models, and partial correlation analyses were used to evaluate associations. Propensity score matching was performed for sensitivity analyses. Results: Overall, 309 patients (69.8%) were born AGA, 80 (18.1%) were born SGA, and 54 (12.2%) were born LGA. Compared with AGA counterparts, CPP girls born SGA were more prone to have elevated HbA1c (adjusted OR = 4.54; 95% CI, 1.43-14.42) and low HDL cholesterol (adjusted OR = 2.33; 95% CI, 1.18-4.61). In contrast, being born LGA was not associated with increased risk for any glucose or lipid derangements. Despite the fact that elevated CMR score was more common among individuals born LGA than AGA (adjusted OR = 1.84; 95% CI, 1.07-4.35), no significant difference was found on non-obesity CMR score (adjusted OR = 0.75; 95% CI, 0.30-1.88). When controlling for age, birth weight SDS, and current BMI-SDS, individuals with high DHEAS exhibited higher HDL cholesterol and apolipoprotein A-1 concentrations and lower triglyceride level and non-obesity CMR score. Furthermore, DHEAS correlated positively with HDL cholesterol and apolipoprotein A-1 and negatively with triglyceride, prominently in girls born SGA, after adjustments for the three abovementioned confounders. Sensitivity analyses corroborated the findings. Conclusion: Among CPP girls, those born SGA were more likely to possess cardiometabolic risk factors compared to their AGA peers. The difference we observed in cardiometabolic risk between individuals born LGA and AGA was driven by BMI. High DHEAS was associated with favorable lipid profile in CPP girls, even in subjects born SGA. [ABSTRACT FROM AUTHOR]

Premature adrenarche is often linked to a cluster of endocrine-metabolic risk factors. Our objective was to explore the association of dehydroepiandrosterone sulfate (DHEAS) levels at age 7 with cardio-metabolic traits at ages 10 and 13, independently of adiposity and pubertal stage. Longitudinal study of 603 individuals (301 girls/302 boys) from the Generation XXI birth cohort. DHEAS at age 7 was measured by immunoassay. Anthropometrics, pubertal staging, blood pressure, and metabolic outcomes were evaluated at ages 7, 10, and 13. Pearson correlations between DHEAS and cardio-metabolic traits (insulin, HOMA-IR, triglycerides, LDL-cholesterol, high-sensitivity C-reactive protein, and systolic and diastolic blood pressure) were computed. Path analysis was used to estimate the effect of DHEAS at age 7 on cardiometabolic traits at ages 10 and 13, adjusted for body mass index (BMI) z-score and Tanner stage. DHEAS at age 7 correlated positively with insulin and HOMA-IR at ages 7 and 10 in both sexes, and at age 13 in girls, but not in boys. In girls, DHEAS levels at age 7 directly influenced HOMA-IR at age 13, controlling for BMI and Tanner stage. In boys, DHEAS at age 7 did not influence HOMA-IR at ages 10 and 13. DHEAS at age 7 did not influence the other cardio-metabolic outcomes analyzed. DHEAS levels in mid-childhood have a positive longitudinal association with on insulin-resistance that persists, in girls, but not in boys, at least until age 13. No association was found regarding dyslipidemia, hypertension, or low-grade inflammation. [ABSTRACT FROM AUTHOR]

PurposeMost patients with prostate cancer receiving enzalutamide or abiraterone develop resistance. Clinical evidence indicates that serum levels of dehydroepiandrosterone sulfate (DHEAS) and biologically active DHEA remain in the high range despite antiandrogen treatment. The conversion of DHEAS into DHEA by steroid sulfatase (STS) may contribute to sustained intracrine androgen synthesis. Here, we determine the contribution of STS to treatment resistance and explore the potential of targeting STS to overcome resistance in prostate cancer.Experimental designSTS expression was examined in patients and cell lines. In vitro, STS activity and expression were modulated using STS-specific siRNA or novel STS inhibitors (STSi). Cell growth, colony formation, androgen production, and gene expression were examined. RNA-sequencing analysis was conducted on VCaP cells treated with STSi. Mice were treated with STSis with or without enzalutamide to determine their effects in vivo.ResultsSTS is overexpressed in patients with castration-resistant prostate cancer (CRPC) and resistant cells. STS overexpression increases intracrine androgen synthesis, cell proliferation, and confers resistance to enzalutamide and abiraterone. Inhibition of STS using siRNA suppresses prostate cancer cell growth. Targeting STS activity using STSi inhibits STS activity, suppresses androgen receptor transcriptional activity, and reduces the growth of resistant C4-2B and VCaP prostate cancer cells. STSis significantly suppress resistant VCaP tumor growth, decrease serum PSA levels, and enhance enzalutamide treatment in vitro and in vivo.ConclusionsThese studies suggest that STS drives intracrine androgen synthesis and prostate cancer proliferation. Targeting STS represents a therapeutic strategy to treat CRPC and improve second-generation antiandrogen therapy.

Abstract Introduction Neuropsychiatric symptoms are important treatment targets in the management of dementia and can be present at very early clinical stages of neurodegenerative diseases. Increased cortisol has been reported in Alzheimer’s disease (AD) and has been associated with faster cognitive decline. Elevated cortisol output has been observed in relation to perceived stress, depression, and anxiety. Dehydroepiandrosterone sulfate (DHEAS) has known anti-glucocorticoid effects and may counter the effects of cortisol. Objectives We aimed to examine whether CSF cortisol and DHEAS levels were associated with (1) neuropsychiatric symptoms at baseline, (2) changes in neuropsychiatric symptoms over 3 years, and (3) whether these associations were related to or independent of AD pathology. Methods One hundred and eighteen participants on a prospective study in a memory clinic setting, including patients with cognitive impairment (n = 78), i.e., mild cognitive impairment or mild dementia, and volunteers with normal cognition (n = 40), were included. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). CSF cortisol and DHEAS, as well as CSF AD biomarkers, were obtained at baseline. Neuropsychiatric symptoms were re-assessed at follow-up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline neuropsychiatric symptoms, the presence of AD pathology as indicated by CSF biomarkers, and CSF cortisol and DHEAS. We used repeated-measures mixed ANCOVA models to examine the associations between the neuropsychiatric symptoms’ changes over time, baseline CSF cortisol and DHEAS, and AD pathology. Results Higher CSF cortisol was associated with higher NPI-Q severity scores at baseline after controlling for covariates including AD pathology status (B = 0.085 [0.027; 0.144], p = 0.027; r = 0.277). In particular, higher CSF cortisol was associated with higher baseline scores of depression/dysphoria, anxiety, and apathy/indifference. Elevated CSF cortisol was also associated with more marked increase in NPI-Q scores over time regardless of AD status (p = 0.036, η 2 = 0.207), but this association was no longer significant after controlling for BMI and the use of psychotropic medications. CSF DHEAS was associated neither with NPI-Q scores at baseline nor with their change over time. Cortisol did not mediate the association between baseline NPI-Q and changes in clinical dementia rating sum of boxes over 36 months. Conclusion Higher CSF cortisol may reflect or contribute to more severe neuropsychiatric symptoms at baseline, as well as more pronounced worsening over 3 years, independently of the presence of AD pathology. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms in patients with dementia.

Background. According to the literature data, long-term and poorly controlled hypertension (HTN) leads to target organs damage, and in some cases, to the development of associated diseases, the severity of which in men may be partly due to the characteristics of the androgenic status.The aim: to reveal the features of hormonal indicators of androgen status and their relationship with the anthropometric and metabolic characteristics of the therapeutic clinic male patients, depending on the severity of HTN.Materials and methods. 296 men aged 59,0 [54,0; 65,0] years with confirmed HTN were examined. All study participants in the morning on an empty stomach underwent anthropometry, determination of metabolic and androgenic status, and assessment of comorbid burden. Depending on the severity of hypertension, all patients were divided into two groups (G): G1 (n = 134) – patients with hypertension without a history of coronary artery disease or stroke; G2 (n = 162) – patients with hypertension with a history of ischemic heart disease (IHD) and/or stroke.Results. In male patients of G2 with severe HTN, a decrease in the levels of free testosterone (FT) and, to a greater extent, dehydroepiandrosterone sulfate (DHEA-S), as well as total cholesterol, high and low density lipoproteins, was revealed. The correlation analysis performed revealed statistically significant negative correlations between the levels of total testosterone (TT) and FT with body mass index, the value of the ratio of waist circumference to hips, only the level of FT – with the presence of IHD, chronic heart failure (CHF), disorders of carbohydrate metabolism and abdominal type of fat distribution, and the level of DHEA-S – with the presence of IHD and CHF.Conclusion. A decrease in FT and DHEA-S is associated with early progression of atherosclerosis and the risk of developing HTN-associated cardiovascular events, which can aggravate the course of HTN.

Using Spearman's rank correlation we studied the correlations between the serum dehydroepiandrosterone-sulfate (DHEA-S) concentration and the concentration of testosterone, thyroid-stimulating hormone, thyroxine, triiodothyronine, insulin, and cortisol in the indigenous and newcomer population of the Yamalo-Nenets Autonomous Okrug. A positive correlation was found between the DHEA-S concentration and testosterone in indigenous women and newcomers. A stronger correlation was found in the group of newcomer women. In indigenous men, DHEA-S was positively correlated with cortisol. The newcomer men showed a positive correlation between DHEA-S and thyroid-stimulating hormone. No correlations were found between the concentration of DHEA-S with insulin, thyroxine, and triiodothyronine in any of the examined groups. [ABSTRACT FROM AUTHOR]

Background: Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease with multiple and complex pathogenic mechanisms. Currently, renal biopsy is considered the gold standard for diagnosing membranous nephropathy. However, there were limitations to the renal puncture biopsy, such as the relatively high cost, longer time consuming, and the risk of invasive procedures. We investigated the profile of serum metabolites in IMN patients based on the UHPLC-QE-MS metabolomics technique for exploring the potential disease biomarkers and clinical implementation. Methods: In our research, we collected serum samples from healthy control (n = 15) and IMN patients (n = 25) to perform metabolomics analysis based on the UHPLCQE-MS technique. Result: We identified 215 differentially expressed metabolites (DEMs) between the IMN and healthy control (HC) groups. Furthermore, these DEMs were significantly identified in histidine metabolism, arginine and proline metabolism, pyrimidine metabolism, purine metabolism, and steroid hormone biosynthesis. Several key DEMs were significantly correlated with the level of clinical parameters, such as serum albumin, IgG, UTP, and cholesterol. Among them, dehydroepiandrosterone sulfate (DHEAS) was considered the reliable diagnostic biomarker in the IMN group. There was an increased abundance of actinobacteria, phylum proteobacteria, and class gammaproteobacterial in IMN patients for host-microbiome origin analysis. Conclusion: Our study revealed the profiles of DEMs from the IMN and HC groups. The result demonstrated that there were disorders of amino acids, nucleotides, and steroids hormones metabolism in IMN patients. The down-regulation of DHEAS may be associated with the imbalance of the immune environment in IMN patients. In host-microbiome origin analysis, the gut microbiota and metabolite disturbances were present in IMN patients. [ABSTRACT FROM AUTHOR]

Dehydroepiandrosterone-sulfate (DHEAS) is an adrenal androgen that is, in part, aromatized to estradiol. It continues to be produced after menopause and provides estrogenicity after depletion of ovarian hormones. Estradiol depletion contributes to memory circuitry changes over menopause, including changes in hippocampal (HIPP) and dorsolateral- and ventrolateral-prefrontal cortex (DLPFC; VLPFC) function. Further, major depressive disorder (MDD) patients have, in general, lower levels of estradiol and lower DHEAS than healthy controls, thus potentially a higher risk of adverse menopausal outcomes. We investigated whether higher DHEAS levels after menopause is associated with better memory circuitry function, especially in women with MDD. 212 adults (ages 45-55, 50% women) underwent clinical and fMRI testing. Participants performed a working memory (WM) N-back task and an episodic memory verbal encoding (VE) task during fMRI scanning. DHEAS levels were significantly associated with memory circuitry function, specifically in MDD postmenopausal women. On the WM task, lower DHEAS levels were associated with increased HIPP activity. On the VE task, lower DHEAS levels were associated with decreased activity in the HIPP and VLPFC. In contrast, there was no association between DHEAS levels and memory circuitry function in MDD pre/perimenopausal women, men, and non-MDD participants regardless of sex and reproductive status. In fact, MDD postmenopausal women with higher levels of DHEAS were similar to MDD pre/perimenopausal women and men. Thus, memory circuitry deficits associated with MDD and a lower ability of the adrenal gland to produce DHEAS after menopause may contribute to a lower ability to maintain intact memory function with age.

BackgroundTransient hypothalamic-pituitary-adrenal axis dysfunction occurs in critically ill foals with sepsis and neonatal maladjustment syndrome (NMS). Cortisol is the most commonly measured steroid. However, a complex interaction of various steroid compounds might play a role in pathophysiology of this disorder.ObjectiveTo identify steroid compounds present at high concentrations at birth that rapidly and steadily decrease within the first 7 days of life in healthy foals and that might be supportive diagnosis of NMS and other neonatal disorders.AnimalsTen healthy neonatal Quarter Horse foals (5 females and 5 males).MethodsProspective study. Blood was collected in heparinized tubes within 30 minutes after birth, and at 12, 24, 48, 72, 96, 120, 144, and 168 hours of age. Plasma was separated and a panel of steroid compounds was analyzed using liquid chromatography-mass spectrometry. A nonlinear regression model was used to determine decay concentrations over time. Confidence intervals (CIs) were calculated and significance was set a P ≤ .05.ResultsFive compounds were identified: pregnenolone, progesterone, deoxycorticosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Pregnenolone and progesterone concentrations rapidly decreased by 24 hours of age and remained low throughout the first 7 days of life. Their half-life (95% CI) was short at 3.7 (3.4, 4.0) and 4.5 (2.8, 6.1) hours, respectively. No statistical differences in the concentrations of these compounds were found between males and females.Conclusions and clinical relevanceProgesterone might be a useful marker for identifying continuous endogenous production of neuroactive steroids in foals with suspected NMS and other neonatal diseases.

The androgen precursors, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are produced in high amounts by the adrenal cortex primarily in humans and a few other primates. The human adrenal also secretes 11-oxygenated androgens (11-oxyandrogens), including 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT), of which 11OHT and 11KT are bioactive androgens. The 11-oxyandrogens, particularly 11KT, have been recognized as biologically important testicular androgens in teleost fishes for decades, but their physiological contribution in humans has only recently been established. Beyond fish and humans, however, the presence of 11-oxyandrogens in other species has not been investigated. This study provides a comprehensive analysis of a set of C19 steroids, including the traditional androgens and 11-oxyandrogens, across 18 animal species. As previously shown, serum DHEA and DHEAS were much higher in primates than all other species. Circulating 11-oxyandrogens, especially 11KT, were observed in notable amounts in male, but not in female trout, consistent with gonadal origin in fish. The circulating concentrations of 11-oxyandrogens ranged from 0.1 to 10 nM in pigs, guinea pigs and in all the primates studied (rhesus macaque, baboon, chimpanzee and human) but not in rats or mice, and 11OHA4 was consistently the most abundant. In contrast to fish, serum 11KT concentrations were similar in male and female primates for each species, despite significantly higher circulating testosterone in males, suggesting that 11KT production in these species is not testis-dependent and primarily originates from adrenal-derived 11-oxyandrogen precursors.

Study objectiveDehydroepiandrosterone (DHEA) and its sulfated form (DHEAS)-jointly referred to as DHEA(S)-are neurosteroids known to regulate brain development and function that have been found to be positively correlated with cognitive function. It is unknown whether prechemotherapy plasma DHEA(S) levels are associated with the onset of cancer-related cognitive impairment (CRCI). The objective of this study was to evaluate whether an association exists between prechemotherapy plasma DHEA(S) levels and onset of CRCI in patients with breast cancer receiving chemotherapy.DesignMulticenter, prospective cohort study.SettingTwo specialized cancer centers in Singapore.PatientsEighty-one patients with early-stage breast cancer (stages I-III) who had no prior exposure to chemotherapy and/or radiotherapy and were scheduled to receive anthracycline-based or taxane-based chemotherapy treatment with curative intent.Measurements and main resultsPatients completed assessments for self-perceived and objective cognitive function at three time points: prechemotherapy (T1), during chemotherapy (T2), and after chemotherapy (T3). Plasma samples were collected prior to chemotherapy, and DHEA(S) levels were quantified by using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable logistic regression was used to adjust for clinically important factors and to evaluate the association between prechemotherapy plasma DHEA(S) levels and CRCI. Mean ± SD age was 48.9 ± 9.3 years, with 27.8% of patients experiencing clinically significant cognitive impairment based on global Functional Assessment of Cancer Therapy-Cognitive Function scores. The mean ± SD prechemotherapy plasma DHEAS and DHEA levels were 1.61 ± 0.91 μmol/L and 19.21 ± 13.13 nmol/L, respectively. Prechemotherapy DHEAS levels were found to be associated with impairment in the self-perceived cognitive domains of verbal fluency (adjusted odds ratio [OR] 0.27, 95% confidence interval [CI] 0.08-0.96) and mental acuity (adjusted OR 0.25, 95% CI 0.08-0.74). Conversely, DHEA levels were not associated with impairment in any cognitive subdomains.ConclusionOur findings suggest that patients with higher prechemotherapy DHEAS levels had lower odds of developing self-perceived cognitive impairment. Future studies are required to further investigate the effect of DHEA(S) on specific cognitive domains and to validate our findings in independent cohorts.

Low blood dehydroepiandrosterone sulfate (DHEAS) levels have strong positive associations with stroke and coronary heart disease. However, it is unclear whether DHEAS is independently associated with cardiovascular risk factors. Therefore, we examined the association between cardiovascular risk factors and DHEAS concentration among a high-risk population of Latinos (Puerto Ricans aged 45 to 75 years at baseline) in a cross-sectional analysis of the Boston Puerto Rican Health Study. Of eligible participants, 72% completed baseline interviews and provided blood samples. Complete data were available for 1355 participants. Associations between cardiovascular risk factors (age, sex, total cholesterol, high-density lipid cholesterol, triglycerides, and glucose) and log-transformed DHEAS (μg/dL) were assessed. In robust multivariable regression analyses, DHEAS was significantly inversely associated with age (β = -12.4; 95% CI: -15.2, -9.7; per 5 years), being female (vs. male) (β = -46; 95% CI: -55.3, -36.6), and plasma triglyceride concentration (β = -0.2; 95% CI: -0.3, -0.1; per 10 mg/dL) and was positively associated with total cholesterol and plasma glucose levels (β = 1.8; 95% CI: 0.6, 3 and β = 0.2; 95% CI: 0.04, 0.3, respectively, per 10 mg/dL) after adjustment for smoking, alcohol, and physical activity and for postmenopausal hormone use in women. Estimates were unchanged after adjustment for measures of chronic disease and inflammation. Women exhibited a stronger age-related decline in DHEAS and a positive association with glucose in contrast to findings among men (P interaction < 0.05). In conclusion, in this large study of Latinos with a heavy cardiovascular risk factor burden, we observed significant associations between cardiovascular disease (CVD) risk factors and DHEAS, with variations by sex. These findings improve our understanding of the role DHEAS may play in CVD etiology.

Objective　We aimed to explore the correlation between androgen level and TCM constitution in patients with early-onset androgenetic alopecia (AGA). Methods　Early-onset AGA patients who visited the Hair Medical Center of the China-Japan Friendship Hospital between November 2020 and April 2021 were selected. The clinical baseline data were collected, and the serum levels of testosterone (T), sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate ( DHEAS) were determined. The TCM constitution questionnaire was filled out, and TCM constitution identification was carried out. The patients who have effectively completed the TCM constitution questionnaire and serum test were divided into groups, first according to the main constitution, and then according to the composite constitution with the binary classification. The analysis of variance, nonparametric test, and multivariate linear regression analysis were used to analyze the correlation between androgen level and TCM constitution. Results　220 patients with early-onset AGA were enrolled. Among them, 195 patients completed the questionnaire and underwent serum test. Among 195 patients in the main constitution, the top four were damp heat constitution ( 25. 64%), balanced constitution ( 21. 03%), qi stagnation constitution ( 16. 41%) and yang deficiency constitution ( 11. 28%). The total frequency of the composite constitution is 310 times, and the top four are damp heat constitution (22. 58%), qi stagnation constitution (16. 77%), balanced constitution (13. 23%) and yang deficiency constitution (12. 26%). In the main constitution grouping method, the serum SHBG level of patients with yang deficiency constitution was higher than that of patients with damp heat constitution (P<0. 05). The serum DHEAS level of patients with phlegm dampness constitution, qi stagnation constitution and yang deficiency constitution were lower than those with damp heat constitution (P<0. 05,P<0. 01). The serum DHEAS level of patients with yin deficiency constitution and damp heat constitution were higher than those with balanced constitution (P<0. 01). The serum DHEAS level of patients with qi stagnation constitution and yang deficiency constitution were lower than those with yin deficiency constitution (P<0. 05, P<0. 01). In the composite constitution grouping method, multivariate linear regression analysis showed that T was positively correlated with male and yang deficiency constitution. SHBG was negatively correlated with male, BMI, degree of AGA, and damp heat constitution; DHEAS was positively correlated with male, BMI, and damp heat constitution and negatively correlated with age, balanced constitution and phlegm dampness constitution. Conclusion　The serum levels of T, SHBG, and DHEAS in patients with early-onset AGA are related to the TCM constitution. Androgen plays a key role in many systemic diseases, and the study of TCM constitution can provide a new way to explain the correlation. This study suggests that we should pay attention to the recuperation of patients with different TCM constitutions, the comprehensive intervention of serum androgens and other endocrine hormones, and the possibility of subsequent complications of other systemic diseases with early-onset AGA. [ABSTRACT FROM AUTHOR]

Background. Clinical trials showed a number of additional phenotypes of metabolic syndrome. All of them differ in the type of metabolic disorders and the composition of subcutaneous and visceral adipose tissue. Some of phenotypes have a number of clinical and metabolic similarities with endogenous or exogenous hypercorticism syndromes. The purpose was to characterize the functional activity of the adrenal glands in type 2 diabetes depending on the phenotypic features: the degree of general obesity and the level of visceral fat. Material and methods. Our trial included 89 patients with type 2 diabetes (46 men and 43 women) aged 32 to 85 years. The examination included evaluation of anthropometric parameters, body composition by the bioelectrical impedance method, assessment of the lipid and carbohydrate metabolism, the level of cortisol, dehydroepiandrosterone sulfate (DHEAS) in blood serum, and the activity of 11-beta-hydroxysteroid dehydrogenase (11β-HSD) enzyme. Results. Insulin and C-peptide levels were significantly lower in the non-obese group. The cortisol/DHEAS ratio was elevated in both subgroups with high levels of visceral fat as possible marker of imbalance of anabolic and catabolic hormones. In addition, the concentration of the cortisol, measured in the blood serum of the patients after waking up, was within the normal range. However, the average value in both groups was closer to its upper ranges. This may suggest the presence of subclinical hypercortisolism caused by an increased activity of 11β-HSD, which contributes to the local production of cortisol in visceral adipose tissue. Conclusions. The hormonal and metabolic changes that we found in our groups of patients with type 2 diabetes may indicate anabolic-catabolic imbalance, which is manifested both in the features of the topography of adipose tissue and in changes of metabolic processes, i.e. form the special metabolic phenotype with a catabolic or anabolic axis. Detection the subgroups at high risk allows to develop pathogenetic approaches to the most targeted comprehensive correction of existing violations. [ABSTRACT FROM AUTHOR]

Introduction: Neuropsychiatric symptoms are important treatment targets in the management of dementia and can be present at very early clinical stages of neurodegenerative diseases. Increased cortisol has been reported in Alzheimer's disease (AD) and has been associated with faster cognitive decline. Elevated cortisol output has been observed in relation to perceived stress, depression, and anxiety. Dehydroepiandrosterone sulfate (DHEAS) has known anti-glucocorticoid effects and may counter the effects of cortisol. Objectives: We aimed to examine whether CSF cortisol and DHEAS levels were associated with (1) neuropsychiatric symptoms at baseline, (2) changes in neuropsychiatric symptoms over 3 years, and (3) whether these associations were related to or independent of AD pathology. Methods: One hundred and eighteen participants on a prospective study in a memory clinic setting, including patients with cognitive impairment (n = 78), i.e., mild cognitive impairment or mild dementia, and volunteers with normal cognition (n = 40), were included. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). CSF cortisol and DHEAS, as well as CSF AD biomarkers, were obtained at baseline. Neuropsychiatric symptoms were re-assessed at follow-up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline neuropsychiatric symptoms, the presence of AD pathology as indicated by CSF biomarkers, and CSF cortisol and DHEAS. We used repeated-measures mixed ANCOVA models to examine the associations between the neuropsychiatric symptoms' changes over time, baseline CSF cortisol and DHEAS, and AD pathology. Results: Higher CSF cortisol was associated with higher NPI-Q severity scores at baseline after controlling for covariates including AD pathology status (B = 0.085 [0.027; 0.144], p = 0.027; r = 0.277). In particular, higher CSF cortisol was associated with higher baseline scores of depression/dysphoria, anxiety, and apathy/indifference. Elevated CSF cortisol was also associated with more marked increase in NPI-Q scores over time regardless of AD status (p = 0.036, η2 = 0.207), but this association was no longer significant after controlling for BMI and the use of psychotropic medications. CSF DHEAS was associated neither with NPI-Q scores at baseline nor with their change over time. Cortisol did not mediate the association between baseline NPI-Q and changes in clinical dementia rating sum of boxes over 36 months. Conclusion: Higher CSF cortisol may reflect or contribute to more severe neuropsychiatric symptoms at baseline, as well as more pronounced worsening over 3 years, independently of the presence of AD pathology. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms in patients with dementia. [ABSTRACT FROM AUTHOR]

Hyperandrogenism (HA) remains an actual problem that raises a large number of questions, in particular, in cases of discrepancy between the clinical signs of HA and biochemical parameters. This review includes an analysis of recent studies of androgen synthesis and metabolism in healthy women of reproductive age; management of pathologies accompanied by HA; as well as contemporary approaches to the principles of prescribing and evaluating the results of the main available markers of biochemical HA. There are сoncepts of clinical and biochemical HA. Biochemical HA is an increase in the levels of various circulating androgens. The concept of clinical HA includes hirsutism as assessed by the modified Ferriman–Gallwey scale. The most common causes of HA include polycystic ovary syndrome, non-classical forms of congenital adrenal hyperplasia, other endocrine disorders. It is necessary to carry out a differential diagnosis of these conditions with more rare causes as a primarily tumor pathology. The choice and evaluation of laboratory markers of biochemical HA should be made taking into account clinical data such as puberty history, anovulation, polycystic ovarian morphotype, obesity; presence and degree of hirsutism and/or other androgen-associated dermatopathies, the characteristics of the course of clinical HA (sudden onset, rapid progression), presence of other endocrinopathies, liver and kidney dysfunction; diabetes mellitus. The objectives of the laboratory assessment of HA are determination of HA severity; determination of the source of excess androgen synthesis (ovaries, adrenal glands); assessment of the free fraction of circulating active androgens; in some cases, assessment of the formation of active androgens in the skin. The following indicators are used to solve the tasks in laboratory diagnostics: total testosterone, free testosterone, free androgen index, androstenedione, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, dihydrotestosterone. A comprehensive assessment of these indicators allows not only assessing the presence of HA and its severity, but also the nature of its leading and secondary components, which determine the presence and prognosis of metabolic risks and allow individualizing therapeutic approaches.

The purpose of the study was to investigate the association of carriage of rs9939609 polymorphism in the FTO gene with features of androgen status in men.Material and methods. The observational one-stage examination of 139 male patients aged 22 to 69 years, admitted to a therapeutic hospital in a planned manner has been carried out in the Clinic of the Federal Research Center for Fundamental and Translational Medicine in the period 2020–2021. All fasting men in the morning (8:00–8:30) were carried out of an anthropometric examination to determine physical development, sampling of venous blood from the cubital vein to assess the hormonal parameters of androgen status, and taking a sample of the buccal epithelium for molecular genetic research. Based on the carriage of the rs9939609 (T>A) polymorphism of the FTO gene, the following groups (G) of patients were distinguished: G1 – wild-type homozygotes (WT/WT), G2 – heterozygotes (WT/A), G3 – homozygotes for the mutant allele (A/A).Results and discussion. The statistically significant differences were found in the levels of total testosterone between G1 and G3 (11.6 vs 14.5 nmol/L, p = 0.010), as well as free testosterone in G1 compared to G2 (0.233 vs 0.287 nmol/L, p = 0.012) and G3 (0.233 vs 0.321 nmol/L, p = 0.002) when analyzing the clinical-anthropometric and hormonal features of the androgen status of the examined male patients in the selected groups. Assessment of the association revealed statistically significant positive correlations between the carriage of the mutant allele and the levels of total (r = 0.247; p = 0.013) and free (r = 0.296; p = 0.003) testosterone, and negative - with the frequency of androgen deficiency according to the free testosterone criteria (r = –0.240; p = 0.016).Conclusions. It has been shown that the carriage of the A/A genotype of rs9939609 polymorphism of the FTO gene is associated with an increase in the levels of total and free testosterone, that indicates a protective effect against the development of androgen deficiency in men. The obtained results suggest that this effect is due to the epigenetic effect of the FTO gene protein product on the expression of other genes involved in the synthesis of androgens in the gonads, but also in the adrenal cortex since no association of the carriage of the rs9939609 polymorphism of the FTO gene with the DHEA-C level was found.

Dehydroepiandrosterone sulfate (DHEAS) is a steroid molecule whose function and mechanism of action in the human body are still inadequately researched. A potential protective function for the cardiovascular system can be explained by activation of nitric oxide production, impact on endothelial and mitochondrial function, and inhibition of proinflammatory cytokine production (IL-6 and TNF-α). Some research shows the beneficial effects of DHEA/DHEAS on many bodily functions, especially in the cardiovascular and the neurological systems. However, we need to be careful with interpretation of the results because of different criteria used for defining arterial hypertension, the race that was observed, and reproductive status of women, as these factors can change the conclusion. Due to a lack of evidence, DHEAS supplementation is still not recommended. We need multicentric prospective and randomized studies on DHEAS to examine its potential impact on blood pressure regulation and cardiovascular risk.

Hyperemesis gravidarum is a condition wich characterized by severe nausea and vomiting in the first half of pregnancy. Etiological factors are hormonal, metabolic, immunological, genetic and psycho-emotional changes during pregnancy. Objective. To assess the anxiety and depression status of women with hyperemesis gravidarum in relation to cortisol and dehydroepiandrosterone sulfate (DHEA-C). Materials and methods. This study involved 163 pregnant women: the main group – 109 patients with hyperemesis gravidarum, the control group – 54 pregnant women without vomiting. The level of anxiety was assessed on the scale of reactive and personal anxiety by Spielberg – Hanin, the state of depression by Beck Depression Scale, the cortisol and DHEA-C plasma blood levels were performed by enzyme-linked immunosorbent assay. Results. A high levels of both situational in 55.0% of women and personal anxiety in 60.6% (2.9 and 2.5 – fold higher compared control group (in both cases p

Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. Although skeletal muscle disorders are often found in diabetic people, the clinical significance of DHEAS in skeletal muscle remains unclear. Therefore, we aimed to determine whether DHEAS is associated with the development of skeletal muscle disorders in individuals with type 2 diabetes (T2D). A cross-sectional study was conducted in 361 individuals with T2D. Serum DHEAS levels, skeletal muscle mass index (SMI), handgrip strength (HS), and gait speed (GS) were measured in the participants. Pre-sarcopenia, sarcopenia, and dynapenia were defined according to the definitions of the AWGS 2019 criteria. DHEAS level was positively associated with HS but not with SMI or GS after adjustment of confounding factors. Multiple logistic regression analyses in total subjects showed that DHEAS level had an inverse association with the prevalence of dynapenia but not with the prevalence of pre-sarcopenia or sarcopenia. Furthermore, a significant association between DHEAS level and dynapenia was found in males but not in females. ROC curve analysis indicated that cutoff values of serum DHEAS for risk of dynapenia in males was 92.0 μg/dL. Therefore, in male individuals with T2D who have low serum levels of DHEAS, adequate exercise might be needed to prevent dynapenia.

ObjectiveTo evaluate factors associated with incident self-reported vaginal dryness and the consequences of this symptom across the menopausal transition in a multiracial/ethnic cohort of community-dwelling women.MethodsWe analyzed questionnaire and biomarker data from baseline and 13 approximately annual visits over 17 years (1996-2013) from 2,435 participants in the Study of Women's Health Across the Nation, a prospective cohort study. We used discrete-time Cox proportional-hazards regression to identify predictors of incident vaginal dryness and to evaluate vaginal dryness as a predictor of pain during intercourse and changes in sexual intercourse frequency.ResultsThe prevalence of vaginal dryness increased from 19.4% among all women at baseline (ages 42-53 years) to 34.0% at the 13th visit (ages 57-69 years). Advancing menopausal stage, surgical menopause, anxiety, and being married were positively associated with developing vaginal dryness, regardless of partnered sexual activity. For women not using hormone therapy, higher concurrent levels of endogenous estradiol were inversely associated (multivariable-adjusted hazard ratio: 0.94 per 0.5 standard deviation increase, 95% confidence interval: 0.91-0.98). Concurrent testosterone levels, concurrent dehydroepiandrosterone sulfate levels, and longitudinal change in any reproductive hormone were not associated with developing vaginal dryness. Both vaginal dryness and lubricant use were associated with subsequent reporting of pain during intercourse, but not with a decline in intercourse frequency.ConclusionIn these longitudinal analyses, our data support many clinical observations about the relationship between vaginal dryness, menopause, and pain during intercourse, and suggest that reporting of vaginal dryness is not related to androgen level or sexual intercourse frequency.

Allostatic load (AL) exposure may cause detrimental effects on the neuroendocrine system, leading to metabolic syndrome (MetS). The primary mediators of AL involve serum dehydroepiandrosterone sulfate (DHEAS; a functional HPA axis antagonist); further, cortisol, urinary norepinephrine (NE), and epinephrine (EPI) excretion levels (assessed within 12-h urine as a golden standard for the evaluation of the HPA axis activity and sympathetic nervous system activity). However, the evidence of an association between the primary mediators of AL and MetS is limited. This systematic review aimed to critically examine the association between the primary mediators of AL and MetS. PubMed and Web of Science were searched for articles from January 2010 to December 2021, published in English. The search strategy focused on crosssectional and case–control studies comprising adult participants with MetS, obesity, overweight, and without chronic diseases. The STROBE checklist was used to assess study quality control. Of 770 studies, twenty-one studies with a total sample size (n = 10,666) met the eligibility criteria. Eighteen studies were cross-sectional, and three were case–control studies. The included studies had a completeness of reporting score of COR % = 87.0 ± 6.4%. It is to be noted, that cortisol as a primary mediator of AL showed an association with MetS in 50% (urinary cortisol), 40% (serum cortisol), 60% (salivary cortisol), and 100% (hair cortisol) of the studies. For DHEAS, it is to conclude that 60% of the studies showed an association with MetS. In contrast, urinary EPI and urinary NE had 100% no association with MetS. In summary, there is a tendency for the association between higher serum cortisol, salivary cortisol, urinary cortisol, hair cortisol, and lower levels of DHEAS with MetS. Future studies focusing on longitudinal data are warranted for clarification and understanding of the association between the primary mediators of AL and MetS. [ABSTRACT FROM AUTHOR]

Artificial receptors for hydrophobic molecules usually have moderate affinities and limited selectivities. We describe three new classes of high affinity hydrophobic receptors for nonaromatic steroids based on deoxyribonucleotides, obtained through five high stringency selections coupled with tailored counter-selections. The isolation of multiple classes of high affinity steroid receptors demonstrates the surprising breadth of moderately sized hydrophobic binding motifs (

We aimed to explore longitudinal changes in androgen levels in individuals with spinal cord injury (SCI) within initial inpatient rehabilitation stay and identify clinical/injury characteristics associated with hormone levels. Linear regression analysis was applied to explore the association between personal/injury characteristics and androgen hormones (total testosterone, free testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S)) at admission to rehabilitation. Longitudinal changes in androgen levels were studied using linear mixed models. Analyses were stratified by sex and by injury type. We included 70 men and 16 women with SCI. We observed a non-linear association between age, time since injury, and androgens at baseline. At admission to initial rehabilitation, mature serum SHBG (full-length, protein form which lacks the N-terminal signaling peptide) was higher, while DHEA and DHEA-S were lower among opioid users vs. non-users. Serum levels of total testosterone and DHEA-S increased over rehabilitation period [β 3.96 (95%CI 1.37, 6.56), p = 0.003] and [β 1.77 (95%CI 0.73, 2.81), p = 0.01], respectively. We observed no significant changes in other androgens. Restricting our analysis to men with traumatic injury did not materially change our findings. During first inpatient rehabilitation over a median follow up of 5.6 months, we observed an increase in total testosterone and DHEA-S in men with SCI. Future studies need to explore whether these hormonal changes influence neurological and functional recovery as well as metabolic parameters during initial rehabilitation stay. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most common and second most deadly type of cancer worldwide, with approximately 1.9 million cases and 0.9 million deaths worldwide in 2020. Previous studies have shown that estrogen and testosterone hormones are associated with colorectal cancer risk and mortality. However, the potential effect of their precursor, dehydroepiandrosterone sulfate (DHEAS), on colorectal cancer risk has not been investigated. Therefore, evaluating DHEAS's effect on colorectal cancer will expand our understanding of the hormonal contribution to colorectal cancer risk. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal effect of DHEAS on colorectal cancer. We obtained DHEAS and colorectal cancer genomewide association study (GWAS) summary statistics from the Leipzig Health Atlas and the GWAS catalog and conducted MR analyses using the TwoSampleMR R package. Our results suggest that higher DHEAS levels are causally associated with decreased colorectal cancer risk (odds ratio per unit increase in DHEAS levels z score = 0.70; 95% confidence interval [0.51, 0.96]), which is in line with previous observations in a case-control study of colon cancer. The outcome of this study will be beneficial in developing plasma DHEAS-based biomarkers in colorectal cancer. Further studies should be conducted to interpret the DHEAS-colorectal cancer association among different ancestries and populations. [ABSTRACT FROM AUTHOR]

The sigma-1 receptor (S1R) is involved in intracellular lipid synthesis and transport. Recent studies have shown that its genetic inactivation impairs adipogenic differentiation in vitro. This study investigated the role of S1R in adipose tissue physiology and metabolic health using adult and old WT and S1R KO mice. Visceral fat mass was increased in adult, but not old S1R-KO male mice compared to that of WT mice, despite having similar body weights, food intake, and energy expenditure. The average adipocyte size was 64 % larger in adult KO mice than in adult WT mice. Adult S1R-KO mice showed reduced plasma dehydroepiandrosterone sulfate (DHEA-S) and elevated fasting plasma leptin concentrations. Lipidomic analysis revealed alterations in plasma metabolite concentrations, particularly reduced levels of sphingomyelins, ceramides, phosphatidylcholines, lysophosphatidylcholines, and cholesteryl esters in adult mice. Decreased expression of Pparγ, Adipoq, and Atgl was detected in visceral white adipose tissue (vWAT) isolated from adult KO mice. Additionally, Fabp4 and Adipoq expression levels were significantly lower in KO adipose-derived stromal cells than in WT adipose-derived stromal cells. A fivefold increase in the mitochondrial fatty acid oxidation rate and a 43 % increase in electron transfer coupling capacity were detected in adult S1R-KO vWAT. In summary, our investigation revealed an age-dependent association between increased visceral adiposity and decreased plasma levels of DHEA-S in S1R-deficient male mice. These findings underscore the potential role of S1R in regulating metabolic processes in adipose tissue and suggest that DHEA-S is a potential mediator of adiposity changes in the absence of S1R., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Frailty is characterized by vulnerability and decline in physical, mental, and social activity, significantly contributing to adverse health outcomes. Frailty encompasses nutritional status, muscle strength, inflammation, and hormones. Dehydroepiandrosterone sulfate (DHEAS) is one of the hormones hypothesized to play a role in frailty. Handgrip strength (HGS) correlates with overall muscle strength. The fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale can be used to readily screen frailty. Identifying markers associated with frailty can facilitate its early diagnosis, risk stratification, and target interventions to prevent or mitigate its negative consequences. This study sought to evaluate the associations between frailty, HGS, and DHEAS in a Portuguese frailty unit (FU)., Methods: We developed an observational retrospective study in an FU. Patients admitted to the FU underwent a rehabilitation program. We assessed frailty with the FRAIL scale. We assayed DHEAS upon admission to the FU. We measured HGS at admission (i-HGS) and discharge (f-HGS). We also considered HGS variation (∆ HGS) and length of stay., Results: Out of 119 subjects, 97 fulfilled the eligibility criteria (mean age 78.35 ± 9.58 years; 44.33% men). Overall, 88 (90.72%) patients had a FRAIL scale score of 3 or more. DHEAS values were not significantly different in either the categories of the FRAIL scale or frailty status. DHEAS values were also not significantly correlated with either i-HGS, f-HGS, ∆ HGS, age, or FU length of stay. Frail patients had a significantly lower i-HGS (p = 0.002) and f-HGS (p = 0.001) and a significantly higher length of stay (p = 0.006). Also, the i-HGS and f-HGS significantly decreased with the increase of the FRAIL scale score (p < 0.0001 for both). The cut-off values of the i-HGS and the f-HGS for detecting frail patients in our study were 13.3 kg and 19.1 kg, respectively (p < 0.0001 for both). The i-HGS was significantly and independently associated with the frailty status of frail (p = 0.001), with a 15% probability reduction of a patient being frail for every kilogram increase in the i-HGS., Conclusion: Frail patients assessed with the FRAIL scale had a significantly lower i-HGS and f-HGS and a higher length of stay. In this study, we found frailty and DHEAS to be not associated and DHEAS values to be not correlated with i-HGS or f-HGS. In our opinion, the creation of an FU with an initial FRAIL scale screening and HGS measurement might have a significant impact on identifying frail people and ensuring the implementation of a multimodal multidisciplinary approach., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of the Autonomous Region of Madeira Health Care System issued approval nº38/2022. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Caires et al.)

Allostatic load (AL) exposure may cause detrimental effects on the neuroendocrine system, leading to metabolic syndrome (MetS). The primary mediators of AL involve serum dehydroepiandrosterone sulfate (DHEAS; a functional HPA axis antagonist); further, cortisol, urinary norepinephrine (NE), and epinephrine (EPI) excretion levels (assessed within 12-h urine as a golden standard for the evaluation of the HPA axis activity and sympathetic nervous system activity). However, the evidence of an association between the primary mediators of AL and MetS is limited. This systematic review aimed to critically examine the association between the primary mediators of AL and MetS. PubMed and Web of Science were searched for articles from January 2010 to December 2021, published in English. The search strategy focused on cross-sectional and case–control studies comprising adult participants with MetS, obesity, overweight, and without chronic diseases. The STROBE checklist was used to assess study quality control. Of 770 studies, twenty-one studies with a total sample size (n = 10,666) met the eligibility criteria. Eighteen studies were cross-sectional, and three were case–control studies. The included studies had a completeness of reporting score of COR % = 87.0 ± 6.4%. It is to be noted, that cortisol as a primary mediator of AL showed an association with MetS in 50% (urinary cortisol), 40% (serum cortisol), 60% (salivary cortisol), and 100% (hair cortisol) of the studies. For DHEAS, it is to conclude that 60% of the studies showed an association with MetS. In contrast, urinary EPI and urinary NE had 100% no association with MetS. In summary, there is a tendency for the association between higher serum cortisol, salivary cortisol, urinary cortisol, hair cortisol, and lower levels of DHEAS with MetS. Future studies focusing on longitudinal data are warranted for clarification and understanding of the association between the primary mediators of AL and MetS.